5-alkenyl and 5-alkynyl indole compounds
Described herein are compounds selective for 5-HT.sub.1D -like receptors, which have the general formula: ##STR1## wherein: R.sup.1 is selected from H, aryl and aryl substituted with 1, 2 or 3 substituents independently selected from loweralkyl, loweralkoxy, loweralkylcarbonyl, loweralkyl-S--, loweralkyl-S(O)--, loweralkyl-SO.sub.2 -, S.dbd.C.dbd.N--, O.dbd.C.dbd.N--, halo, loweralkoxycarbonyl, nitro, amino, loweralkyl-NH--, (loweralkyl).sub.2 --N--, loweralkyl-SO.sub.2 -loweralkyl-;A is a double or triple bond;R.sup.2 is selected from a group of Formula II, III, IV and V: ##STR2## R.sup.3 is selected from H and loweralkyl; R.sup.4 is selected from H and loweralkyl;One of R.sup.5 and R.sup.6 is H and the other is independently selected from H, loweralkoxy, loweralkyl and hydroxy; andR.sup.7 and R.sup.8 are independently selected from H and loweralkyl or R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form an optionally substituted 3- to 6-membered ring;or a salt, solvate or hydrate thereof.Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of the 5-HT.sub.1D -like receptor is implicated, such as migraine.
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Claims
1. A compound according to Formula I: ##STR34## wherein: R.sup.1 is selected from the group consisting of H, aryl and aryl substituted with 1, 2 or 3 substituents independently selected from the group consisting of loweralkyl, loweralkoxy, loweralkylcarbonyl, loweralkyl-S--, loweralkyl-S(O)--, loweralkyl-SO.sub.2 -,S.dbd.C.dbd.N--, O.dbd.C.dbd.N--, halo, loweralkoxycarbonyl, nitro, amino, loweralkyl-NH--, (loweralkyl).sub.2 -N--, and loweralkyl-SO.sub.2 -loweralkyl-;
- A is --CH.dbd.CH-- or --C.ident.C-- (a vinyl or alkynyl group)
- R.sup.2 is selected from the group consisting of Formula II, III, IV and V: ##STR35## R.sup.3 is H or loweralkyl; R.sup.4 is H or loweralkyl;
- one of R.sup.5 and R.sup.6 is H and the other is independently selected from the group consisting of H, loweralkoxy, loweralkyl and hydroxy; and
- R.sup.7 and R.sup.8 are independently selected from the group consisting of H and loweralkyl or R.sup.7 and R.sup.8, form an alkylene bridge which, together with the nitrogen atom to which they are attached, creates an unsubstituted or substituted 3- to 6-membered ring;
2. A compound according to claim 1, wherein R.sup.1 is H.
3. A compound according to claim 1, wherein R.sup.1 is selected from the group consisting of phenyl, thienyl, and imidazolo, wherein R.sup.1 is either unsubstituted or substituted with 1, 2 or 3 substituents independently selected from the group consisting of loweralkyl, loweralkoxy, loweralkylcarbonyl, loweralkyl-S--, loweralkyl-SO.sub.2, S.dbd.C.dbd.N--, halo, loweralkoxycarbonyl, nitro, loweralkyl-SO.sub.2 -loweralkyl- and pyrrolo.
5. A compound according to claim 2, wherein A is vinyl.
6. A compound according to claim 1, wherein R.sup.2 is a group of Formula II.
7. A compound according to claim 6, wherein R.sup.3 is methyl.
8. A compound according to claim 1, wherein R.sup.2 is a group of Formula III.
9. A compound according to claim 8, wherein R.sup.4 is methyl.
10. A compound according to claim 1, wherein R.sup.2 is a group of Formula IV.
11. A compound according to claim 10, wherein R.sup.5 and R.sup.6 are both H.
12. A compound according to claim 11, wherein R.sup.7 and R.sup.8 are both methyl.
13. A compound according to claim 10, wherein R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a pyrrolidine ring.
14. A compound according to claim 1, wherein R.sup.2 is a group of Formula V.
15. A compound according to claim 14, wherein R.sup.5 and R.sup.6 are both H.
20. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and, in an amount effective to stimulate a 5-HT.sub.1D -like receptor, a compound as defined in claim 1.
22. A pharmaceutical composition according to claim 21, wherein said compound is one in which R.sup.1 is H.
23. A pharmaceutical composition according to claim 22, wherein said compound is one in which A is vinyl.
24. A pharmaceutical composition according to claim 20, wherein said compound is one in which R.sup.2 is a group of Formula III and R.sup.4 is methyl.
25. A pharmaceutical composition according to claim 20, wherein said compound is one in which R.sup.2 is selected from the group consisting of Formula IV and Formula V.
26. A pharmaceutical composition according to claim 25, wherein said compound is one in which R.sup.5 and R.sup.6 are both H.
27. A pharmaceutical composition according to claim 26, wherein said compound is one in which R.sup.7 and R.sup.8 are both methyl.
28. A pharmaceutical composition according to claim 26, wherein said compound is one in which R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a pyrrolidine ring.
29. A method for treating a patient having a medical condition for which a 5-HT.sub.1D -like receptor agonist is indicated, comprising the step of administering to the patient a pharmaceutical composition as defined in claim 20.
30. A method for treating a patient according to claim 29, wherein the medical condition is migraine.
4870085 | September 26, 1989 | Glaser et al. |
5348968 | September 20, 1994 | Lavielle et al. |
5496957 | March 5, 1996 | Glennon |
5504101 | April 2, 1996 | Glennon |
02037351B | August 1990 | JPX |
WO 9402477 | February 1994 | WOX |
WO 9424127 | October 1994 | WOX |
WO 9617842 | June 1996 | WOX |
- Glen, et al. Journal of Medicinal Chemistry, 1995, 38:3566-3580. "Computer-Aided Design and Synthesis of 5-Substituted Tryptamines and Their Pharmacology at the 5-HT1D Receptor: Discovery of Compounds with Potential Anti-Migraine Properties".
Type: Grant
Filed: Dec 16, 1996
Date of Patent: Jan 5, 1999
Assignee: Allelix Biopharmaceuticals Inc. (Mississauga)
Inventors: Oingchang Meng (Georgetown), Abdelmalik Slassi (Mississauga), Louise Edwards (Mississauga), Sumanas Rakhit (Misssissauga)
Primary Examiner: Floyd D. Higel
Law Firm: Nikaido, Marmelstein, Murray & Oram LLP
Application Number: 8/767,322
International Classification: C07D40302; C07D20902; C07D20904; C07D20916; A61K 31415; A61K 31405;